Lead poisoning remains a significant public health problem. The most devastating effects are observed in the young in the form of encephalopathy and mental retardation. Morphologic evidence suggests that lead exerts a vasculopathic action on cerebral and cerebellar capillaries resulting in a breakdown of the blood-brain barrier (BBB) and the development of brain edema. Both the capillary endothelial cell and its basement membrane are integral parts of the BBB and are the most promising sites for the study of the mechanisms of lead-induced brain edema. Based upon lead effects in extravascular tissues, inhibition of energy metabolism, calcium transport, adenyl cyclase activity and collagen biosynthesis in brain microvessels may underlie the cytotoxic action of lead. These functions will be examined using newly developed techniques for isolation of brain capillaries and purified basement membranes in control and lead-poisoned calves, an unexploited model of lead encephalopathy. This investigation should increase our understanding of lead toxicity and, in addition, add fundamental knowledge of the blood-brain barrier and the development of brain edema.